Modified release preparations are those that provide an in vivo release profile (a ‘modified release’) of an active ingredient, such as a pharmaceutically active ingredient, that is different from the in vivo release profile of the active ingredient without the modification (an ‘immediate release’). The modified release may be such as a delayed, extended, pulsed or sustained release. The modification of the release may be desired for a number of reasons, such as for minimising the side effects of the drug or for decreasing the frequency of dosing to improve patient compliance.
As with all pharmaceutical preparations, an important aspect of the manufacture of modified release preparations is their stability over extended periods of time, which is often referred to as ‘shelf life’. Typically, a preparation's shelf life is linked to two aspects; firstly, the stability of the ingredients themselves, namely the maintenance of their chemical, microbiological, therapeutic and toxicological properties over time; and secondly, the maintenance over time of the originally intended rate of drug release from the dosage form. The present invention is directed towards this second aspect of stability.
All pharmaceuticals must have an appropriate shelf life, being the time for which it can be guaranteed that the preparation has the same properties that it had at the time it was manufactured. These properties may be such as impurity content, drug degradants or rate of drug release. For oral preparations, this shelf life is usually at least 18 months.
However, it has been found for some modified release preparations that, after storage, the release profile alters by a significant amount. For example, some delayed release preparations that have been formulated with an enteric coating so as to release only small amounts of active (10% or less) after 20 minutes might release up to 80% of active by 20 minutes after the preparation has been stored. This increase in rate of release can detract from the utility and effectiveness of the product.
It is an aim of the present invention to provide a modified release preparation that is stable, in that the release profile after storage of a preparation in accordance with the invention will be substantially the same as the release profile of the preparation before storage.